Single-cell RNA sequencing depicts metabolic changes in children with aplastic anemia

Qin Zhou; Lifen Huang; Yong Liu; Junbin Huang; Luping Wen; Jing Yang; Jintang Liang; Yun Chen; Chun Chen

doi:10.3389/fonc.2023.1075408

Single-cell RNA sequencing depicts metabolic changes in children with aplastic anemia

Front Oncol. 2023 Mar 29:13:1075408. doi: 10.3389/fonc.2023.1075408. eCollection 2023.

Authors

Qin Zhou¹, Lifen Huang¹, Yong Liu¹, Junbin Huang¹, Luping Wen¹, Jing Yang¹, Jintang Liang¹, Yun Chen¹, Chun Chen¹

Affiliation

¹ Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China.

Abstract

Introduction: Aplastic anemia (AA) is a bone marrow hematopoietic failure syndrome mediated by immune cells. The mechanism of this immune disorder is not well understood and therapeutic strategies still need to be improved.

Methods: Studies have found that abnormalities in metabolisms promote the survival of AA cells. In recent years, an increasing number of studies have reported the immunosuppressive therapy for the treatment of AA. In this study, we analyzed the transcriptome of AA from peripheral blood compared with healthy donors by single-cell sequencing and identified the affected metabolic pathways including lysine degradation. We demonstrated that the metabolic abnormalities of T lymphocytes mainly focus on glycolysis/gluconeogenesis. In addition, the metabolic abnormalities of natural killer cells concentrated in oxidative phosphorylation.

Results: The key genes involved in abnormal metabolic processes were Neustein neurotrophic factor (NENF), inositol polyphosphate-4-phosphatase type II B (INPP4B), aldo-keto reductase family 1, member C3 (AKR1C3), and carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 2 (CHST2) by differential gene expression analysis.

Discussion: Molecule interaction analysis showed that tumor necrosis factor superfamily, member 12 (TNFSM12) in tumor necrosis factor (TNF) signaling was broadly activated in AA. In conclusion, we suppose that the treatment of the immune cells' abnormal metabolic pathway may contribute to the development of novel strategies to treat AA.

Keywords: NENF; NK cells; T lymphocytes; aplastic anemia (AA); cell metabolism; scRNA seq.

Grants and funding

The work was supported by Pediatric Hematological Oncology, Seventh Affiliated Hospital, Sun Yat-sen University. We also thank Shenzhen Basic Research Project (Natural Science Fund) (202103243003611) to support the design of the study, Shenzhen Science and Technology Innovation Commission (JCYJ20190814164601648 and JCYJ20210324123003009) to support sample collection and analysis, Sanming Project of Medicine in Shenzhen (No. SZSM202011004) and Free Exploration Project of Shenzhen Science and Technology Innovation Commission (JCYJ20180307150419435) to support the manuscript preparation and publication.